Genetic variation of the alpha-1-antitrypsin gene is associated with increased autoantibody production in rheumatoid arthritis

Objective: To examine the prevalence of alpha-1 antitrypsin (AAT) deficiency (AATD) in rheumatoid arthritis (RA), and to determine if AATD is associated with higher levels of rheumatoid factor (RF), antinuclear antibodies (ANA) and anti-citrullinated peptide auto-antibodies (ACPA). Methods: RF, ANA and ACPA were measured by standard immunoturbidimetry, immunofluorescence and ELISA, respectively. Characterisation of AAT phenotypes was performed by isoelectric focussing and immunofixation. Chi-square with Yates' correction and Mann-Whitney U test were used to assess prevalence of alleles associated with AATD in RA and to compare means of antibody titres, respectively. Results: Of 246 individuals with RA, 24 heterozygous AATD individuals were identified, with no statistical significance in the prevalence of AATD in RA and the general population recorded (p=0.39). A positive association between AATD heterozygosity and the production of ACPA was observed (p<0.0001) with increased ACPA titres recorded in the AATD RA cohort compared to the RA group (p=0.01). Conclusion: AATD heterozygous status in RA is strongly associated with positive ACPA and may define a distinct subset of patients with increased severity of disease. This article is protected by copyright. All rights reserved.